Endocrinology of Cardiovascular Function is a fitting inauguration to the Endocrine Update Series. The aim of these publications is to provide the clinician with cutting edge, yet succinct, access to the latest advances in endocrinology. Historically, our understanding of hormonal disturbances was restricted to the classical secretory glands and their targets. As Endocrinology of Cardiovascular Function so aptly indicates, endocrinology is no longer constrained by our early physiologic understanding of glandular disorder. Endocrinology of Cardiovascular Function has set the standard of excellence for the future volumes in this series. Shlomo Melmed, M.D. Series Editor, Endocrine Update Growth factors such as IGF-1 play important roles in cardiovascular cell hypertrophy and the response to acute vascular injury. From another perspective, traditional endocrine hormones, such as estrogen, have been found to participate in preventing the development of atherosclerosis in women, acting through novel mechanisms on target vascular cells. Other `endocrine' hormones, such as PTHRP and adrenomedullin, also modulate cardiovascular and renovascular dynamic states, suggesting new roles for these peptides as vasodilators. This multi-authored text is dedicated to highlighting emerging and important new information regarding the endocrinology of the cardiovascular system. Ellis R. Levin, M.D.

This volume will explore the epidemiology and the basic mechanisms of each of these prenatal phenomena, in an attempt to explain the role of the prenatal environment in promoting postnatal weight gain. This information will contribute to resolving the nature-nurture controversy. This information provides guidance to clinical practitioners involved in both prenatal and postnatal care. This volume further stimulates research into underlying mechanisms and prevention and treatment of this phenomenon.

Amenorrhea: A Case-Based Clinical Guide is a comprehensive review of the current knowledge regarding normal female reproductive physiology. Replete with interesting case vignettes and providing diagnostic algorithms and therapeutic strategies for amenorrhea, Amenorrhea: A Case-Based Clinical Guide is divided into three sections. The first section is composed of two chapters that provide a thorough review of basic science and clinical knowledge about the organ systems responsible for normal physiology of the menstrual cycle. The second section includes discussion about menstrual cycle disruption as it relates to hypothalamic-pituitary dysfunction, surgical and natural menopause, genetic defects, premature ovarian failure/insufficiency and the effects of caloric excess and restriction. The third section offers an update on the physiological effects of prolonged amenorrhea induced surgically or by hypothalamic dysfunction and also includes an original chapter that focuses solely on the impact of race and ethnicity on the prevalence and diagnosis of amenorrhea. Amenorrhea: A Case-Based Clinical Guide brings together chapters from renowned experts who offer state-of-the-art, clinically useful information in a case-based, reader-friendly fashion. This title will be a welcome addition to the bookshelves of all clinicians who practice in women's health settings.

The human pancreas consists of two organs in one: the exocrine gland made up of pancreatic acinar cells and duct cells that produce digestive enzymes and sodium bicarbonate, respectively; the endocrine gland made up of four islet cells, namely alpha-, beta-, delta- and PP-cells that produce glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. While the physiological role of exocrine p- creas is to secrete digestive enzyme responsible for our normal digestion, absorption and assimilation of nutrients, the endocrine pancreas is to secrete islet peptide h- mones maintaining our glucose homeostasis. The pancreatic functions are nely regulated by neurocrine, endocrine, paracrine and/or intracrine mechanisms. Thus, dysregulation of these pathways should have signi cant impacts on our health and disease. Nevertheless, the underlying mechanisms by which pancreatic functions are regulated remain poorly understood. Recent basic science and clinical studies con rm myriad physiological and pathophysiological roles of the tissue renin-angiotensin systems (RAS). Of parti- lar interest is the recent identi cation of a local and functional RAS in the pancreas, which in uences both its exocrine and endocrine function. Its role in the pat- genesis of pancreatic diseases including diabetes and pancreatitis is increasingly recognized, as is the therapeutic potential of RAS antagonism: RAS blockade l- its disease progression of type 2 diabetes mellitus and impaired glucose tolerance, and may also protect against pancreatic in ammation.

Leading researchers comprehensively translate all the latest scientific information regarding endocrine physiology and development into an understanding of the clinical pathogenesis, diagnosis, and treatment of endocrine disease. Organized by endocrine system, each section of the book concisely describes the chronological development of the human organism, from the fetal/prenatal period through childhood, adolescence, and in some cases, into adulthood. The prenatal sections review recent discoveries concerning transcription factors, homeobox genes, and human molecular mutations-the basic processes governing prenatal development of the individual endocrine organs-and detail the pathophysiology, clinical characteristics, and treatment of pediatric endocrine disorders.

Experimental and clinical researchers from a wide range of disciplines present a wealth of fresh scientific information on the biochemistry, molecular biology, pharmacology, and clinical activity of SERMs. The basic science chapters of the book focus-with an eye to the development of the ideal SERM-on the complex mechanisms of estrogen action, including ligand-dependent conformational changes in alpha and beta, and the recruitment of co-activators and co-repressors which modulate the estrogen receptor transcriptional activity and contribute to its crosstalk with growth factor signaling. The clinical presentation reviews the data accumulated on currently available SERMs, primarily tamoxifen and raloxifene, in cancer treatment and prevention, as well as their effects on the reproductive, vascular, skeletal, and central nervous systems. A tentative approach to menopause-related health issues is also provided for women with and without a previous diagnosis of localized breast cancer.

Growth Hormone and the Heart endeavors to bring together knowledge that has been accumulated in the area of GH and the heart, from basic to clinical studies, by research groups working on this topic throughout the world. Lessons from different experimental models and from several human diseases (acromegaly, adult GH deficiency, heart failure) suggest to endocrinologists and cardiologists that GH may not only have a role in the physiology and pathophysiology of heart function, but that GH itself may have a place in the treatment of primary heart diseases (such as dilated cardiomyopathy) or of cardiac complications of hypopituitarism. Growth Hormone and the Heart will be a useful update of the research produced in the field of cardiovascular endocrinology. The Editors also hope that this book will serve as the primary step in the recognition of the wide physiological and clinical significance of GH and heart interactions.

The discovery of mammalian nitric oxide (NO-) synthesis from I-ar- ginine has led to profound increases in our understanding of basic physiological and pathophysiological processes. This understanding has been achieved by major advances in several areas. Three major ni- tric oxide synthase (NOS) isoforms have been identified at the protein and gene level and their specific tissue localization has been linked to processes subject to regulation by NO-. The molecular basis for the di- verse effects of NO- on cell function has been shown to derive from its chemical reactivity with oxygen-containing species and both heme and non-heme iron-dependent enzymes. The potential regulation of heme- dependent enzymes such as cytochromes P450, guanylate cyclase, cy- clooxygenase, and mitochondrial cytochrome oxidase continues to emerge as a key area in NO- research. In addition, it has become clear that the expression of NOS isoforms and NO- release from cells is subject to regulation by sexual steroids and that, in tum, NO- has the potential to regulate steroid biosynthesis via inhibition of cytochromes P450 involved in steroidogenesis. These recent observations on interactions between the NO-/NOS and cytochrome P450/sexual steroid pathways have important implica- tions for understanding fundamental mechanisms involved in endocri- nological processes. They are also likely to lead to novel insights and novel therapeutic approaches for the management of pathophysiologi- cal conditions associated with alterations in sexual steroid hormones.

Changes in the allocation of healthcare resources have raised issues related to the efficacy and outcomes of medical therapy and how such factors may be measured. The questions associated with the quality of life and functional capability of patients with chronic health conditions have been of special interest. Endocrine disorders have the potential for disrupting the general health and well-being of affected individuals and their families; thus they warrant serious attention. This symposium was convened in November 1997 at Palm Beach Gardens, Florida, to bring together medical, behavioral, and social scientists. The meeting fostered the presentation and discussion of the most current clinical research on the effects of various therapies on a wide range of endocrine disorders from diabetes to adrenal insufficiency and growth hormone deficiency. The participants, all noted national and international experts in their fields, focused their attention on both the biomedical value and effectiveness of treatment, as well as on the impact such treatments have on psychological states such as mood and cognition. Many presentations specifically emphasized the quality of life (QOL) indicators that now regu larly appear in many research protocols and reports. The pioneering work of two clinical researchers was a major highlight of the meeting and an Award of Recognition was presented to Robert Blizzard, M. D. , and John Money, Ph. D. , for their innovative and insightful work in pediatric endocrinology and psychosexual development.

It is an authentic privilege to have the opportunity to assemble and edit a new volume on "Prolactin," the first in several decades to be devoted to this fascinating hormone in all its aspects. The obvious clinical rationale for understanding prolactin (PRL) is the frequent occurrence of prolactinomas, the most common type of pituitary tumor. Fortunately, medical management of prolactinomas can be based on our under standing of the physiology of hypothalamic control of the lactotroph. Armed with this knowledge, therapies for proiactinomas are highly successful and well tolerated. Be cause of the historical and practical importance of knowledge regarding the hypothala mus-Iactotroph axis, the first chapters of this volume are dedicated to reviewing the physiology, development, and cell biology of lactotroph regulation. Chapters focusing on prolactinomas and related clinical issues follow these. PRL is the primary hormone that is responsible for "parental care" in many verte brate species. This reproductive strategy is not unique to mammals, but it has devel oped through evolution to be the central distinguishing feature of the mammalian life cycle. Among the mammals, mice have become the most effective research species in recent years. This can be traced to the development of a wide range of methods for manipulating mouse genetics, and thereby influencing development, physiology and behavior. Mice also provide a profound illustration of the physiological challenges faced in maternity. Female mice undergo a post-partum estrous, and often are both pregnant and lactating simultaneously.

The dramatic recent expansion in genomic information has motivated the development of new approaches to characterize gene expression and function. A critical issue for both basic and clinical endocrinologists is the physiological role of genes involved in regulating endocrine functions. Transgenic technologies allow the translation of genotypic information into specific phenotypes by using gene overexpression or loss of specific gene functions. Murine functional genomics is thus of central importance in modem biomedical endocrine research. Although mice are at present, the preferred mammalian species for genetic manipulations because of the availability of pluripotent embryonic. stem cells and inbred strains and the relatively low breeding and maintenance costs, transgenic rats have also been generated and used to study endocrine physiology. The two basic techniques used in the creation of transgenic animal models are integration of foreign DNA into a fertilized oocyte by random chromosomal insertion and homologous recombination in embryonic stem cells that are then introduced into zygotes. Transgenic mice and rats serve as sophisticted tools to probe protein function, as models of human disease, and as hosts for the testing of gene replacement and other therapies. Embryonic stem cell libraries for mouse gene deletion are being developed, which will make it possible to generate knockout mice rapidly and without the need to analyze gene structure, construct targeting vectors, and screen embryonic stem cell clones. A novel approach to transgenesis for the expression of DNA within adult differentiated neuroendocrine cells in vivo is using viral vectors.

Sex-Steroid Interactions with Growth Hormone presents the proceedings of an international symposium held from October 22-25 in Naples, Florida. The proceedings provide new insights and concepts gained by molecular, cellular and neuroendocrine research into mechanistic interactions of the reproductive and somatotrophic axes. Chapters include discussions of the impact of sex steroids on growth hormone secretion in both children and adults; sex steroids, growth hormone releasing factor, and somatostatin; how sex steroids modulate growth hormone action on target issues; and differential effects of growth hormone secretagogues in men and women. This volume is designed for physicians, scientists and other health professionals interested or trained in clinical and basic endocrinology, growth or reproduction.

The pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) has attracted the interest of our group during the last three decades. As early as 1969, a Nobel Symposium dealing with this topic was organized in Stockholm. This was followed in 1987 by a Nobel Conference devoted to the same subject. The main purpose of these meetings was to bring together the most distinguished scientists from all over the world and present theories on molecular and genetic mechanisms responsible for the development of glucose intolerance in NIDDM. This idea was followed also in the present symposium, "New Concepts in the Pathogenesis of NIDDM," organized with diabetologists from Toronto in Canada. Our purpose is to biannually organize international meetings covering important aspects of dia betes research, hoping that this type of interaction may result in new concepts and treat ment alternatives. For us, participating in this symposium in September 1992, the meeting in Stockholm was very stimulating and innovative. It is a special pleasure that almost all invited lecturers submitted manuscripts. Thus, the publication of the proceedings of the symposium makes it possible for all interested in diabetes research to share new ideas and findings presented at the meeting. Claes-G6ran Ostenson Suad Efendic Mladen V ranic v CONTENTS REGULATION OF INSULIN SECRETION Impaired Glucose-Induced Insulin Secretion: Studies in Animal Models with Spontaneous NIDDM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C. -G. Ostenson, A. Khan, and S. Efendic Perturbation ofIslet Metabolism and Insulin Release in NIDDM. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 WJ. Malaisse 2 Regulation of Cytoplasmic Free Ca+ in Insulin-Secreting Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

This volume contains the edited proceedings of the Totts Gap Colloquium on Diabetes Mellitus, DILEMMAS IN DIABETES. The Collo- quium, lasting two and a half days, was organized mainly as a dia- logue among experts in the field with different disciplinary back- grounds and, to some extent, differing points of view. The effort was to synthesize existing knowledge, reconciling disparate data and interpretation, and pointing up important areas of ignorance. Thus, the book should serve not only as a summary of recent information on diabetes, but as a reliable guide to the practicing physician as he wades through often conflicting etiologic dogmas and therapeutic practices. The Colloquium was made possible through the generous support of the Geigy Pharmaceutical Company and the conscientious and expert coordination of Mr. Oscar Swarth. The participants were: Dr. George F. Cahill, Boston, Massachusetts Dr. Harvey C. Knowles, Cincinnati, Ohio Dr. Rachmiel Levine, Duarte, California Dr. Lelio Orci, Geneva, Switzerland Dr. Norton Spritz, New York, New York Dr. Roger Unger, Dallas, Texas Dr. Robert Williams, Seattle, Washington Dr. Stewart Wolf, Galveston, Texas Dr. Arnold Lazarow and Dr. I. Arthur Mirsky were to have partici- pated, but unfortunately were ill at the time of the meeting. Others in attendance included five medical students, especially selected from medical schools in the Philadelphia/New York area.

Dr. Robert L. Jackson, Professor of Child Health at the Uni versity of Missouri-Columbia, decided to retire from clinical practice in 1977 and the Department of Child Health planned a con ference in his honor. The Thirteenth Annual MidweSt Conference on Endocrinology and Metabolism also was in the planning stages and scheduled for two days in the fall. It seemed appropriate to com bine the two into an expanded three-day conference. In view of Dr. Jackson's international reputation in the study and care of children with diabetes mellitus, the conference topic was not dif ficult to find. Experts in this field were delighted to be asked to speak at a conference in Dr. Jackson's honor. We selected a number of excellent speakers to survey the physiology and pathophy siology of pancreatic hormones and their effects in diabetes mel litus, to discuss current knowledge of the microvascular complica tions of the disease, and to put it all into the proper historical perspective of where we have been and where we are going. We think the conference achieved its objective to pay meaningful trib ute to a distinguished member of the scientific community. As with any conference, the conversion of the presentations and discussions to the printed page is a long and arduous process. Many manuscripts were completed well after the conference and references often are more recent than the date of the conference."

Recent Developments in Graves' Ophthalmopathy offers an overview of the pathogenesis, assessment and management of patients with thyroid-associated eye disease. Each chapter is written by an expert and truly represents the current state of the art on the particular topic. This book can therefore almost be considered a textbook on this enigmatic disorder. Recent Developments in Graves' Ophthalmopathy is designed for all those interested in this disease, including basic scientists, clinical endocrinologists, ophthalmologists, radiotherapists, and orbital surgeons. The book gives a comprehensive overview of all aspects of Graves' ophthalmopathy. Subjects covered include the pathology of Graves' eye disease and the controversial views on its autoimmune pathogenesis; assessment of the eye changes using reliable measurements; medical management of Graves' eye disease with an overview of the many treatment options available to the clinician, including orbital radiotherapy and other immunosuppressive treatments; management of the thyroid disease; and finally, the techniques for performing various surgical procedures, which are explained and illustrated.

The purpose of these volumes is to provide a reference work for the methods of purifying many of the receptors we know about. This becomes increasingly important as full-length recep- tors are overexpressed in bacteria or in insect cell systems. A major problem for abundantly expressed proteins will be their purification. In addition to purification protocols, many other de- tails can be found concerning an individual receptor that may not be available in standard texts or monographs. No book of this type is available as a compendium of purification procedures. Receptor Purification provides protocols for the purification of a wide variety of receptors. These include receptors that bind: neurotransmitters, polypeptide hormones, steroid hormones, and ligands for related members of the steroid supergene family and others including receptors involved in bacterial motion. The text of this information is substantial so as to require its publica- tion in two volumes. Consequently, a division was made by grouping receptors depending upon the nature of their ligands. Thus, in volume 1 there are contributions on serotonin receptors, adrenergic receptors, the purification of GTP-binding proteins, opioid receptors, neurotensin receptor, luteinizing hormone re- ceptor, human chorionic gonadotropin receptor, follicle stimulat- ing hormone receptor, thyrotropin receptor, prolactin receptor, epidermal growth factor receptor, platelet derived growth factor receptor, colony stimulating factor receptor, insulinlike growth factor receptors, insulin receptor, fibronectin receptor, interferon receptor, and the cholecystokinin receptor.

Since the late 1960s, there has been an acceleration of research focused on understanding how the efferent ducts, the epididymis, and the vas deferens function with respect to the maturation and storage of spermatozoa and as hormone dependent tissues. Another major interest in the epididymis is that it is an attractive target for the development of male contraceptives. There are well over 16,000 peer reviewed articles in the literature on these tissues, their structure, gene expression, protein synthesis and function. Regular international meetings have been initiated that are dedicated to this field. Thus, there is an urgent need for a comprehensive reference volume that spans every facet of epididymal biology, from historical background to the most current results, from basic cell and molecular biology to clinical issues. Well-established experts from every part of the world have contributed to this volume. By necessity, each author was given page limitations so that many topics are not dealt with exhaustively. Whenever possible, references to more comprehensive discussion of specific topics are included.

'Morphological imaging' and 'functional imaging' are current mainstays for the diagnosis, successful treatment and accurate follow-up of patients with endocrine disorders. Functional and Morphological Imaging of the Endocrine System provides the reader with comprehensive but concise insights in the application of cutting edge imaging techniques and updated imaging protocols for the diagnosis and treatment of hypersecretory hormonal syndromes and functional endocrine masses.

These Proceedinqs of the Midwest Conference on Endocrinology and Metabolism are being published by Plenum Press for the first time. Earlier Proceedings in the series Vlere published by the University of Missouri at Columbia. The shift to an internationally recognized pub lisher reflects the considerable growth in stature that the Midwest Con ferences have undergone since their inception nine years ago. Originally concerned only with the endocrinology of the thyroid, the Conferences now explore other endocrine areas. Efforts are made to assemble a panel of speakers selected from different sub-disciplines within endocrinology for the purpose of addressing a common problem. The Ninth Conference typifi es til i s approach. The format used in recent Conferences is not unique, but is unfor tunately encountered too rarely. A few prominent scholars are invited to come together to expound their findings and concepts in considerable depth, and to participate in a discussion which, together with the for mal presentation, is published in the Proceedings. The discussion, noted for its unhurried nature, permits wide participation by the audi ence. The subject of the Ninth Conference is one which is basic and im portant not only to endocrinology but also to biology in general. Many, possibly most, life processes change in a rhythmic fashion, with similar states recurring at regular time intervals. This rhythmic property of living systems expresses itself as a recognizable and definable pattern or "time-form" in a manner equivalent to the more customary spatial form."

"Fertility Preservation in Males: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this practical reference guide provides an update on options for fertility preservation in men, while also discussing important related epidemiologic, ethical, medico-legal, psychological, and social aspects. Using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms, the chapters all conform to a uniform structure, including step by step protocol of laboratory procedures, key issues in commentary and a list of references. The result is a unique resource for reproductive endocrinologists, urologists, embryologists, reproductive scientists, and oncologists."

Since the first description of Philadelphia chromosome-negative chronic myeloproliferative disorders more than 100 years ago, the diagnosis and therapy of these conditions have been based primarily on clinical experience and judgement. Until recently very little was known about the molecular basis of these diseases. In order to spark research in this area basic scientists and clinicians from various parts of the world have contributed to this volume, the first of its kind to put together the current knowledge. The book deals with the new WHO classification of these disorders, novel aspects of diagnostic pathology, the search for disease-relevant genes utilizing molecular biology and proteomic techniques, the description of the roles of PVR-1 and VHL genes for polycythemias and the discovery of the gene mutation responsible for the idiopathic hypereosinophilic syndrome. A chapter on anagrelide, an important novel drug for the treatment of primary thrombocythemia, is included.

After a decade or longer, approximately one-third of individuals with either type 1 or type 2 diabetes commence a downhill course in which decreasing renal function and failing vision define a Renal-Retinal Syndrome, dominating all aspects of life and presaging early death. Only a generation ago, survival after onset of end-stage renal disease (ESRD) in diabetes was limited because rehabilitation was preempted by blindness, limb amputation, stroke, and heart disease. By 1998, however, team management has improved the outlook, with preserved sight and return to work and home responsibilities, usually for a decade or longer, following kidney transplantation and laser photocoagulation. Recognition of the critical requirement for blood pressure regulation and metabolic control are central themes in management. In this unique book, the accomplishments of ophthalmologists, nephrologists, diabetologists, transplant surgeons, and basic scientists are blended into a strategic approach that may be readily applied by all those caring for diabetic patients. Each of twenty-one presentations suitable for primary care physicians, as well as for subspecialists concerned with macrovascular and microvascular complications of diabetes, is placed in perspective by an introductory editorial analysis. Promising near-term innovative therapies, including insertion of genetically engineered beta cells or polymer-coated islets of Langerhans, interdiction of kinins that promote retinal angiogenesis, and prevention of synthesis of advanced glycosylated endproducts (AGEs), are presented in detail. While comprehensive care of diabetic patients reflects multiple incremental advances that in sum afford major benefit, this text envisions further remarkable changes likely to suppress and possibly entirely prevent the Diabetic Renal-Retinal Syndrome.

Leading medical specialists critically review for the general practitioner the latest techniques for the clinical management of diabetic neuropathy. These authoritative contributors focus on the practical aspects of diabetic neuropathy and describe in detail the treatments that are currently available or expected to become available in the near future. They also include concise discussions of the causes of diabetic neuropathy and highlight the relatively unknown features of neuropathy that can significantly impact a patient's life. Comprehensive, up-to-date bibliographies at the end of each chapter provide an opportunity for the interested physician to gain a more detailed picture of a particular topic. This book offers family physicians, internists, endocrinologists, podiatrists, cardiologists, neurologists, and gastroenterologists an authoritative practical guide and a vital day-to-day reference source for the management of their neuropathic diabetic patients.

The purpose of these volumes is to provide a reference work for the methods of purifying many of the receptors we know about. This be comes increasingly important as full-length receptors are overexpressed in bacteria or in insect cell systems. A major problem for abundantly expressed proteins will be their purification. In addition to purification protocols, many other details can be found concerning an individual receptor that may not be available in standard texts or monographs. No book of this type is available as a compendium of purification procedures. Receptor Purification provides protocols for the purification of a wide variety of receptors. These include receptors that bind: neurotransmit ters, polypeptide hormones, steroid hormones, and ligands for related members of the steroid supergene family and others, including receptors involved in bacterial motion. The text of this information is substantial, so as to require its publication in two volumes. Consequently, a division was made by grouping receptors by the nature of their ligands. Thus, in Volume One there are contributions on serotonin receptors, adrenergic receptors, the purification of GTP-binding proteins, opioid receptors, neurotensin receptor, luteinizing hormone receptor, human chorionic gonadotropin receptor, follicle stimulating hormone receptor, thyro tropin receptor, prolactin receptor, epidermal growth factor receptor, platelet derived growth factor receptor, colony stimulating factor recep tor, insulin-like growth factor receptors, insulin receptor, fibronectin receptor, interferon receptor, and the cholecystokinin receptor.